This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-ny-nd/3.0/), and is reproduced with permission from Global Advances in Health and Medicine - Global Adv Health Med. 2013;2(5):38-43.

Abstract

Background

A case report is a narrative that describes, for medical, scientific, or educational
purposes, a medical problem experienced by one or more patients. Case reports written
without guidance from reporting standards are insufficiently rigorous to guide clinical
practice or to inform clinical study design.

Methods

We used a three-phase consensus process consisting of (1) pre-meeting literature review
and interviews to generate items for the reporting guidelines, (2) a face-to-face
consensus meeting to draft the reporting guidelines, and (3) post-meeting feedback,
review, and pilot testing, followed by finalization of the case report guidelines.

Conclusions

We believe the implementation of the CARE (CAse REport) guidelines by medical journals
will improve the completeness and transparency of published case reports and that
the systematic aggregation of information from case reports will inform clinical study
design, provide early signals of effectiveness and harms, and improve healthcare delivery.

Keywords:

Introduction

A case report is a detailed narrative that describes, for medical, scientific, or
educational purposes, a medical problem experienced by one or several patients

Case reports present clinical observations customarily collected in healthcare delivery
settings. They have proved helpful in the identification of adverse and beneficial
effects, the recognition of new diseases, unusual forms of common diseases, and the
presentation of rare diseases [1]. For example, our understanding of the relationship between thalidomide and congenital
abnormalities [2] and the use of propranolol for the treatment of infantile hemangiomas began with
case reports [3]. Case reports may generate hypotheses for future clinical studies, prove useful in
the evaluation of global convergences of systems-oriented approaches, and guide the
individualization and personalization of treatments in clinical practice [4,5]. Furthermore, case reports offer a structure for case-based learning in healthcare
education and may facilitate the comparison of healthcare education and delivery across
cultures.

Case reports are common and account for a growing number of articles in medical journals
[6]; however their quality is uneven [7,8]. For example, one study evaluated 1316 case reports from four peer-reviewed emergency-medicine
journals and found that more than half failed to provide information related to the
primary treatment that would have increased transparency and replication [9]. Written without the benefit of reporting guidelines, case reports often are insufficiently
rigorous to be aggregated for data analysis, inform research design, or guide clinical
practice [7,9].

Reporting guidelines exist for a variety of study designs including randomized controlled
trials (Consolidated Standards of Reporting Trials, or CONSORT) [10], observational studies (Strengthening the Reporting of Observational studies in Epidemiology,
or STROBE) [11], and systematic reviews and meta-analyses (Preferred Reporting Items for Systematic
Reviews and Meta-Analyses, or PRISMA) [12]. Empirical evidence suggests that a journal’s adoption of the CONSORT statement as
a guide to authors is associated with an increase in the completeness of published
randomized trials [13]. Guidelines have been developed for adverse-event case reports [14]; however, general reporting guidelines for case reports do not exist. Our primary
objective was to develop reporting guidelines for case reports through a consensus-based
process.

Methods

Research design

We followed the Guidance for Developers of Health Research Reporting Guidelines [15] and developed a three phase consensus process [16]. This consisted of (1) a pre-meeting literature review followed by interviews to
generate items for a case report checklist, (2) a face-to-face consensus meeting for
drafting a reporting guideline, and (3) post-meeting feedback and pilot testing followed
by finalization of the case report guidelines.

Participants

We contacted 28 individuals who fulfilled at least one of four criteria [17-19]: (1) publication of articles related to case reports; (2) publication of a manual,
handbook, or method guidelines related to case reports; (3) publication of a systematic
review of methods or reporting related to case reports; and (4) publication of other
reporting guidelines for clinical research.

Consensus process

Phase 1: Four of the authors, the steering committee (JG, GK, DM, and DR), searched
the literature for publications on the role of case reports, recommendations for their
publication, and surveys on reporting quality. A letter was sent to 28 potential participants
explaining the purpose of the meeting, details of the consensus technique, and requesting
their participation in generating specific recommendations for case reporting. Twenty-seven
people agreed to participate and were scheduled for a telephone interview and sent
a selection of key articles on case reports. During the telephone interview, participants
were asked (1) what information was required to be included in case-reporting guidelines,
(2) the rationale for their suggestions, and (3) for references that supported their
reasoning.

Three of the authors (JG, GK, and DR) grouped the recommendations from the literature
search and interviews by theme together with their rationale, references, and operational
definitions. No quantitative scoring was done.

Phase 2: The face-to-face consensus meeting at the University of Michigan in Ann Arbor
(October 2012) included 18 participants from Phase 1, one research assistant and two
student observers. The meeting began with a review of the blinded recommendations
elicited during the Phase 1 interviews, in whole group and small group sessions. On
the second day, open discussion of each potential item continued, during which clarifications,
opinions, justifications, operational definitions, and new ideas were expressed. By
the end of the second day, the group had agreed upon a set of preliminary reporting
recommendations.

Phase 3: The draft checklist was refined by the steering committee and sent for two
rounds of review to the complete group (Phase 1 and 2 participants). The finalized
reporting guidelines incorporated the feedback from the entire CARE group.

The checklist begins with a statement that describes the narrative of a case report.
The meeting CARE group felt that a case report should tell a story using prose that
has a consistent style across all sections, including the rationale for any conclusions
and take-away messages.

We recommend a timeline (item 7) in the form of a table or figure that gives the specific
dates and times of important components of the case. This might include family and
past medical history, genetic information, current symptoms, diagnostic test results,
interventions, and events that occurred during follow-up. The timeline should show
how the key events of the case unfolded.

We created separate checklist items for diagnostic assessments (item 8) and therapeutic
interventions (item 9) with the recognition that both items will often be relevant
in a case report.

The group discussed at length whether to include the patient’s perspective on his
or her experience. In the end, we advocated for patient-reported outcomes and experiences
whenever possible (item 12). There was also discussion about the need for guidelines
for patient-reported outcomes of their care. In a similar vein, a recent extension
of the CONSORT statement was published for patient-reported outcomes in randomized
trials; CONSORT-PRO [20].

Finally, we included an item on informed consent (item 13). We believe that authors
have an ethical duty to obtain informed consent from the patient to publish patient
information in a case report. Consent becomes informed when the patient or a relative
reads the case report and approves its contents. If the patient cannot give consent
and attempts to find a relative to give proxy consent have failed, the authors should
seek permission to publish from an institutional committee. There may be other circumstances
where an ethics committee or Institutional Review Board (IRB) approval may be necessary.
The CARE guidelines are shown in the following Table 1.

Discussion

This 13-item checklist provides a framework to satisfy the need for completeness and
transparency for published case reports. We attempted to strike a balance between
adequate detail and the concise writing that is one of the appealing characteristics
of a case report. Our consensus process resulted in a set of essential items for authors
to consider when submitting a case report for publication.

While case reports have long been an important source of new ideas and information
in medicine [21], it appears that case reports are likely to begin to play a role in the discovery
of what works and for whom. BioMed Central launched the Journal of Medical Case Reports in 2007 [22] and a Cases Database in 2012 with more than 11,000 published case reports from 50
medical journals. In 6 months, it has grown to more than 26,000 case reports from
212 medical journals [23]. The CARE guidelines checklist is part of a growing effort to improve the reporting
of case reports.

There is substantial empirical evidence that reporting guidelines improve the completeness
of published scientific reports eg, see references [13,24,25]. A recent Cochrane review examining the influence of journal endorsement of the CONSORT
statement on reporting included 53 publications assessing 16,604 randomized controlled
trials and found that CONSORT-endorsing journals consistently have better overall
reporting [13]. However, the potential impact of the CONSORT statement and related reporting guidelines
has not been fully realized. A study examining the instructions to peer reviewers
of 116 health research journals found that only 41 (35%) provided online instructions
to peer reviewers. Of those, only 19 (46%) mentioned or referred to reporting guidelines
as a useful resource [26]. In response, the authors provide several recommendations for editors to improve
the peer review of submitted manuscripts, suggesting that journals have a responsibility
to support peer reviewers [26].

The developers of reporting guidelines have a responsibility to plan a dissemination
and implementation strategy that supports guidelines utilization [15]. Our efforts have several components:

1. The CARE guidelines will be presented at international conferences and workshops
including the Peer Review and Biomedical Publication Congress in Chicago on September
10, 2013.

2. This article will be published simultaneously in multiple medical journals and
outreach to the 212 journals depositing case reports into the BioMed Central Case
Report Database.

3. We will develop a more detailed explanation and elaboration article to outline
the rationale for each item and include empirical evidence and examples of good reporting
from published case reports.

4. The CARE guidelines are being pilot tested, and preliminary results support the
guidelines as currently written (personal communication with Helmut Kiene, Erika Oberg,
Bill Manahan). Guidelines extensions for specialties are being developed.

5. The CARE guidelines and related documents will be available on a dedicated website
(www.CARE-statement.org), the EQUATOR Network website (www.equator-network.org), and
translated into multiple languages.

6. Authors, journal editors, peer reviewers and the wider medical community are encouraged
to use the CARE checklist and provide feedback that can be incorporated into regular
updates of the CARE guidelines.

7. We will conduct and support research into the impact of the CARE guidelines on
the reporting of case reports.

Limitations

The CARE guidelines and their development have several possible limitations. First,
these guidelines were developed through a consensus method and thus represent the
opinions of the participants. However, consensus was easily reached during our meeting,
we referred to the empirical evidence where available, and we received feedback from
a wide selection of individuals, beyond those involved in our consensus meeting. Second,
we recognize that causality determinations are a challenge for case reports even when
following reporting guidelines [27,28]. The CARE guidelines emphasize information quality independent of causality assessments.
Different specialties, practitioners, and patients are likely to require extensions
of the CARE guidelines with specialty specific information. We welcome discussions
with groups interested in using the CARE guidelines as the basis for their specific
reporting needs.

Conclusions

Anticipating a long future for case reports, we have provided guidance in the form
of reporting standards for use by healthcare stakeholders around the world. The growth
of case reports in an era in which clinical trials and systematic reviews dominate
the tables of content of medical journals indicates that case reports have value,
particularly with the increasing importance of individualized care. Unlike randomized
controlled trials, case reports are individual reports related to the care of individual
patients where the sample size is one. When systematically collected and combined
into larger datasets, they can be analyzed, enhancing the early discovery of effectiveness
and harms.

We anticipate that the analysis of systematically aggregated information from patient
encounters (now mandated by some insurance plans) will provide scalable, data-driven
insights into what works for which patients in real time, facilitating comparisons
across medical systems and cultures. Practitioners will soon be able to provide—and
in some cases they are required to provide—patients with information from their encounters.
This will transform how we think about “evidence” and revolutionize its creation,
diffusion, and use—opening new opportunity landscapes. When it becomes clear how new
data contributes to evidence, the stewardship needed to produce high-quality data
will be more rewarding and our attitude toward “observation” will shift. The CARE
guidelines provide a framework to satisfy the need for precision, completeness, and
transparency.

Author contributions

JG, GK, DGA, DM, HS, and DR met the ICMJE criteria for authorship. JG and DR wrote
the first draft of the article. DGA, JG, GK, DM, DR, and HS critically reviewed and
edited drafts. The entire CARE group participated in parts or all of the guidelines
development process and contributed to the editing and revision of the CARE guidelines
and this article. All authors read and approved the final manuscript.

* Participated in the guidelines development process, the review and editing of the
CARE guidelines and this article, but did not attend the face-to-face consensus meeting.

Acknowledgments

Joel Gagnier, University of Michigan, and David Riley, Global Advances in Health and Medicine, organized this consensus-based guideline-development project. The Department of
Orthopaedic Surgery, the Office of the Vice-President of Research at the University
of Michigan, and Global Advances in Health and Medicine® provided funding for this project. David Moher is funded through a University of
Ottawa Research Chair. Funding support was used to reimburse the travel-related expenses
of conference attendees. There were no honoraria. The volunteer steering committee
consisted of Joel J. Gagnier, Gunver Kienle, David Moher, and David Riley. There are
no conflicts of interest to report.